Design, Synthesis, In Silico, and In Vitro Study of Substituted Phenyl Thiazole‐Pyrimidine/Pyridine Containing Derivatives as Anticancer Agents
Bibliographic record
Abstract
Abstract The present study focuses on the design, synthesis, and in silico evaluation of substituted phenyl thiazole‐pyrimidine/pyridine derivatives as potential anticancer agents targeting Epidermal Growth Factor Receptor (EGFR, PDB ID: 1M17). A series of eight novel derivatives ( R1–R8 ) were synthesized and characterized using FT‐IR, 1 H‐NMR, 13 C‐NMR, and LC‐MS. The cytotoxicity of these compounds was assessed using brine shrimp lethality and MTT assays against MDA‐MB‐468 breast cancer cells, revealing that R1 exhibited the highest potency with an IC 50 of 36.93 ± 4.11 µg/mL, followed by R4 . Further, compounds R1 and R4 were evaluated for EGFR inhibition activity. The results confirm that R1 (IC 50 : 22.65 ± 2.01 µM) and R4 (IC 50 : 36.89 ± 3.81 µM) act as EGFR inhibitors, though they are much less potent than erlotinib (IC 50 : 1.09 ± 0.20 µM). Molecular docking studies using AutoDock Vina (Version 1.5.7) demonstrated strong interactions of R1 and R4 with key active site residues LYS A:721 and MET A:742, with binding energies of −8.9 and −8.8 kcal/mol, respectively, outperforming the standard inhibitor Erlotinib (−7.5 kcal/mol). In silico ADME and toxicity predictions revealed that all compounds exhibit high plasma protein binding (PPB > 98.6%) and potential hERG inhibition, indicating cardiotoxicity risks. The study highlights the potential of thiazole‐pyrimidine/pyridine derivatives as EGFR inhibitors, warranting further biological validation and structural optimization to improve their pharmacokinetic and safety profiles.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".